Immunomodulatory Effects of Calcitriol through DNA Methylation Alteration of FOXP3 in the CD4+ T Cells of Mice

  • Mona Oraei ORCID Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
  • Sama Bitarafan ORCID Iranian Center of Neurological Research, Neuroscience Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
  • Seyed Alireza Mesbah-Namin ORCID Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
  • Ali Noori-Zadeh ORCID Department of Clinical Biochemistry, Faculty of Allied Medical Sciences, Ilam University of Medical Sciences, Ilam, Iran.
  • Fatemeh Mansouri ORCID Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  • Karim Parastouei ORCID Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
  • Ali Anissian ORCID Veterinary Pathology Department, Islamic Azad University, Abhar, Iran.
  • Mir Saeed Yekaninejad ORCID Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
  • Maryam Hajizadeh ORCID Department of Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran.
  • Ali Akbar Saboor-Yaraghi ORCID Mail Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran AND Iranian Center of Neurological Research, Neuroscience Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
Keywords:
Calcitriol, Foxp3 protein, Methylation, Regulatory T-lymphocytes, Vitamin D

Abstract

Vitamin D plays a variety of physiological functions, such as regulating mineral homeostasis. More recently, it has emerged as an immunomodulator player, affecting several types of immune cells, such as regulatory T (Treg) cells. It has been reported that vitamin D exerts some mediatory effects through an epigenetic mechanism. In this study, the impacts of calcitriol, the active form of vitamin D, on the methylation of the conserved non-coding sequence 2 (CNS2) region of the forkhead box P3 (Foxp3) gene promoter, were evaluated.
Fourteen C57BL/6 mice were recruited in this study and divided into two intervention and control groups. The CD4+ T cells were isolated from mice splenocytes. The expression of Foxp3, IL-10, and transforming growth factor-beta (TGF-β1) genes were relatively quantified by real-time PCR technique, and the DNA methylation percentage of every CpG site in the CNS2 region was measured individually by bisulfite-sequencing PCR.
Vitamin D Intervention significantly (p<0.05) could increase the expression of Foxp3, IL-10, and TGF-β1 gene in the CD4+ T cells of mice comparing with the control group. Meanwhile, methylation of the CNS2 region of Foxp3 promoter was significantly decreased in three of ten CpG sites in the vitamin D group compared to the control group.
The results of this study showed that vitamin D can engage the methylation process to induce Foxp3 gene expression and probably Treg cytokines profile. Further researches are needed to discover the precise epigenetic mechanisms by which vitamin D modulates the immune system.

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Published
2020-10-18
How to Cite
1.
Oraei M, Bitarafan S, Mesbah-Namin SA, Noori-Zadeh A, Mansouri F, Parastouei K, Anissian A, Yekaninejad MS, Hajizadeh M, Saboor-Yaraghi AA. Immunomodulatory Effects of Calcitriol through DNA Methylation Alteration of FOXP3 in the CD4+ T Cells of Mice. Iran J Allergy Asthma Immunol. 19(5):509-516.
Section
Original Article(s)